Glycosphingolipids (GSL) form a unique amphipathic subclass of glycoconjugates present on the external leaflet of the eukaryote plasma membrane. A variety of functions have been ascribed to glycolipids including intercellular recognition (1), growth regulation (2), differentiation (3) and microbial adhesion.
GSLs have been studied by isolation of purified GSLs and subsequent chemical modifications. An example of such a chemical transformation is the synthesis of deacyl-GSLs, in which GSL function has been investigated by coupling the free amine functionality of the sphingosine to various molecular units, including fatty acids (4-7), cross linkers (7) or fluorescent probes (8, 9). Similarly, although to a lesser extent, some effort has been directed towards the oxidative cleavage of the internal double bond of the sphingosine (10), where the allylic alcohol component of the ceramide is transformed into a .alpha.-hydroxycarboxylate function.
It has been recognized, however, that isolated soluble GSLs do not always retain the binding characteristics of the membrane-bound glycolipid. In fact, solubilized GSLs may have little or no binding affinity for compounds which bind strongly to the membrane-bound GSL. For example, verotoxin, a toxin produced by certain pathogenic bacteria, binds to globotriaosyl ceramide (Gb.sub.3), a GSL which is anchored in the cell membrane by two long, hydrophobic hydrocarbon chains. However, the binding of verotoxin to Gb.sub.3 which has been freed from the membrane is much weaker.
The ability to study interactions between GSLs and compounds or pathogens which bind to GSLs, in the solution phase, therefore requires glycolipid mimics which are soluble, yet retain the binding affinity of membrane-bound naturally-occurring GSLs for toxins and pathogens.